학술논문

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age.
Document Type
Academic Journal
Author
Merid SK; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.; Novoloaca A; Epigenetics Group, International Agency for Research on Cancer, Lyon, France.; Sharp GC; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; Küpers LK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Kho AT; Computational Health Informatics Program, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.; Roy R; Computational Biology And Informatics, University of California, San Francisco, San Francisco, CA, USA.; HDF Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Gao L; Department of Preventive Medicine, University of Southern California, Los Angeles, USA.; Annesi-Maesano I; Sorbonne Université and INSERM, Epidemiology of Allergic and Respiratory Diseases Department (EPAR), Pierre Louis Institute of Epidemiology and Public Health (IPLESP UMRS 1136), Saint-Antoine Medical School, Paris, France.; Jain P; NIHR-Health Protection Research Unit, Respiratory Infections and Immunity, Imperial College London, London, UK.; Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK.; Plusquin M; NIHR-Health Protection Research Unit, Respiratory Infections and Immunity, Imperial College London, London, UK.; Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium.; Kogevinas M; ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.; Allard C; Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CHUS), Sherbrooke, QC, Canada.; Vehmeijer FO; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Kazmi N; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; Salas LA; Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, USA.; Rezwan FI; School of Water, Energy and Environment, Cranfield University, Cranfield, Bedfordshire, MK43 0AL, UK.; Zhang H; Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, USA.; Sebert S; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.; Biocenter Oulu, University of Oulu, Oulu, Finland.; Department of Genomic of Complex diseases, School of Public Health, Imperial College London, London, UK.; Czamara D; Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, Munich, Germany.; Rifas-Shiman SL; Division of Chronic Disease Research Across the Lifecourse (CoRAL), Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.; Melton PE; School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin University, Bentley, Australia.; Curtin/UWA Centre for Genetic Origins of Health and Disease, School of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia.; Lawlor DA; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; Bristol NIHR Biomedical Research Centre, Bristol, UK.; Pershagen G; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.; Centre for Occupational and Environmental Medicine, Stockholm, Stockholm Region, Sweden.; Breton CV; Department of Preventive Medicine, University of Southern California, Los Angeles, USA.; Huen K; Children's Environmental Health Laboratory, University of California, Berkeley, Berkeley, CA, USA.; Baiz N; Sorbonne Université and INSERM, Epidemiology of Allergic and Respiratory Diseases Department (EPAR), Pierre Louis Institute of Epidemiology and Public Health (IPLESP UMRS 1136), Saint-Antoine Medical School, Paris, France.; Gagliardi L; Division of Neonatology and Pediatrics, Ospedale Versilia, Viareggio, AUSL Toscana Nord Ovest, Pisa, Italy.; Nawrot TS; NIHR-Health Protection Research Unit, Respiratory Infections and Immunity, Imperial College London, London, UK.; Department of Public Health & Primary Care, Leuven University, Leuven, Belgium.; Corpeleijn E; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Perron P; Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CHUS), Sherbrooke, QC, Canada.; Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada.; Duijts L; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Nohr EA; Research Unit for Gynaecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.; Bustamante M; ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.; Ewart SL; College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.; Karmaus W; Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, USA.; Zhao S; Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, RTP, Durham, NC, USA.; Page CM; Norwegian Institute of Public Health, Oslo, Norway.; Herceg Z; Epigenetics Group, International Agency for Research on Cancer, Lyon, France.; Jarvelin MR; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.; Biocenter Oulu, University of Oulu, Oulu, Finland.; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK.; Unit of Primary Care, Oulu University Hospital, Oulu, Finland.; Lahti J; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Turku Institute for Advanced Studies, University of Turku, Turku, Finland.; Baccarelli AA; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA.; Anderson D; Telethon Kids Institute, University of Western Australia, Perth, Australia.; Kachroo P; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Relton CL; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; Bristol NIHR Biomedical Research Centre, Bristol, UK.; Bergström A; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.; Centre for Occupational and Environmental Medicine, Stockholm, Stockholm Region, Sweden.; Eskenazi B; Center for Environmental Research and Children's Health (CERCH), University of California, Berkeley, Berkeley, CA, USA.; Soomro MH; Sorbonne Université and INSERM, Epidemiology of Allergic and Respiratory Diseases Department (EPAR), Pierre Louis Institute of Epidemiology and Public Health (IPLESP UMRS 1136), Saint-Antoine Medical School, Paris, France.; Vineis P; MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; Snieder H; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Bouchard L; Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CHUS), Sherbrooke, QC, Canada.; Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada.; Department of medical biology, CIUSSS-SLSJ, Saguenay, QC, Canada.; Jaddoe VW; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Sørensen TIA; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Vrijheid M; ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.; Arshad SH; Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.; The David Hide Asthma and Allergy Research Centre, Newport, Isle of Wight, UK.; Holloway JW; Human Development & Health, Faculty of Medicine, University of Southampton, Southampton, UK.; Håberg SE; Norwegian Institute of Public Health, Oslo, Norway.; Magnus P; Norwegian Institute of Public Health, Oslo, Norway.; Dwyer T; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.; Murdoch Children's Research Institute, Australia Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia.; Binder EB; Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, Munich, Germany.; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA.; DeMeo DL; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Vonk JM; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.; Newnham J; Faculty of Health and Medical Sciences, UWA Medical School, University of Western Australia, Perth, Australia.; Tantisira KG; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Kull I; Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.; Sachs' Children's Hospital, Södersjukhuset, 118 83, Stockholm, Sweden.; Wiemels JL; Center for Genetic Epidemiology, University of Southern California, Los Angeles, USA.; Heude B; INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Research Team on Early life Origins of Health (EarOH), Paris Descartes University, Paris, France.; Sunyer J; ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.; Nystad W; Norwegian Institute of Public Health, Oslo, Norway.; Munthe-Kaas MC; Norwegian Institute of Public Health, Oslo, Norway.; Department of Pediatric Oncology and Hematology, Oslo University Hospital, Oslo, Norway.; Räikkönen K; Norwegian Institute of Public Health, Oslo, Norway.; Oken E; Division of Chronic Disease Research Across the Lifecourse (CoRAL), Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.; Huang RC; Telethon Kids Institute, University of Western Australia, Perth, Australia.; Weiss ST; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Antó JM; ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.; Bousquet J; University Hospital, Montpellier, France.; Department of Dermatology, Charité, Berlin, Germany.; Kumar A; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.; University of Basel, Basel, Switzerland.; Swiss Tropical and Public Health Institute, Basel, Switzerland.; Söderhäll C; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.; Almqvist C; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.; Cardenas A; Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Gruzieva O; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.; Centre for Occupational and Environmental Medicine, Stockholm, Stockholm Region, Sweden.; Xu CJ; University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute Groningen, Groningen, The Netherlands.; Reese SE; Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, RTP, Durham, NC, USA.; Kere J; Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.; Folkhälsa Research Institute, Helsinki, and Stem Cells and Metabolism Research Program, University of Helsinki Finland, Helsinki, Finland.; Brodin P; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.; Department of Newborn Medicine, Karolinska University Hospital, Stockholm, Sweden.; Science for Life Laboratory, Stockholm, Sweden.; Solomon O; Children's Environmental Health Laboratory, University of California, Berkeley, Berkeley, CA, USA.; Wielscher M; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK.; Holland N; Children's Environmental Health Laboratory, University of California, Berkeley, Berkeley, CA, USA.; Ghantous A; Epigenetics Group, International Agency for Research on Cancer, Lyon, France.; Hivert MF; Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CHUS), Sherbrooke, QC, Canada.; Division of Chronic Disease Research Across the Lifecourse (CoRAL), Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.; Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.; Felix JF; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Koppelman GH; University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute Groningen, Groningen, The Netherlands.; London SJ; Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, RTP, Durham, NC, USA.; Melén E; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. erik.melen@ki.se.; Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden. erik.melen@ki.se.; Sachs' Children's Hospital, South General Hospital, Stockholm, Sweden. erik.melen@ki.se.
Source
Publisher: BioMed Central Country of Publication: England NLM ID: 101475844 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-994X (Electronic) Linking ISSN: 1756994X NLM ISO Abbreviation: Genome Med Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children.
Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung.
Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10 - 7 , of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels.
Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.